@article{BoethBiesenHollnageletal.2021, author = {Boeth, Heide and Biesen, Robert and Hollnagel, Jeremias and Herrmann, Sandra and Ehrig, Rainald and Pelli, Lorenzo and Taylor, William R. and Duda, Georg and Buttgereit, Frank}, title = {Quantification of morning stiffness to assess disease activity and treatment effects in rheumatoid arthritis}, series = {Rheumatology}, volume = {60}, journal = {Rheumatology}, number = {11}, doi = {10.1093/rheumatology/keab323}, pages = {5282 -- 5291}, year = {2021}, abstract = {Objectives The clinical parameter "morning stiffness" is widely used to assess the status of rheumatoid arthritis (RA), but its accurate quantitative assessment in a clinical setting has not yet been successful. This lack of individual quantification limits both personalized medication and efficacy evaluation in the treatment of RA. Methods We have developed a novel technology to assess passive resistance of the metacarpophalangeal (MCP) III joint (stiffness) and its Passive Range of Motion (PRoM). Within this pilot study, nineteen female postmenopausal RA patients and nine healthy controls were examined in the evening as well as in the morning of the following day. To verify the specificity of the biomechanical quantification, eleven patients with RA were assessed both prior to and ∼3 h after glucocorticoid therapy. Results While the healthy controls showed only minor changes between afternoon and morning, in RA patients mean±SD PRoM decreased significantly by 18 ± 22\% and stiffness increased significantly by 20 ± 18\% in the morning compared with the previous afternoon. We found a significant positive correlation between RA activity and biomechanical measures. Glucocorticoids significantly increased mean PRoM by 16 ± 11\% and reduced mean stiffness by 23 ± 22\%. Conclusion This technology allowed mechanical stiffness to be quantified in MCP joints, and has demonstrated high sensitivity in respect to disease status as well as medication effect in RA patients. Such non-invasive, low risk, and rapid assessment of biomechanical joint stiffness opens a novel avenue for judging therapy efficacy in patients with RA, and potentially also in other non-RA inflammatory joint diseases.}, language = {en} } @inproceedings{BoethDudaHinzmannetal., author = {Boeth, Heide and Duda, Georg and Hinzmann, Daniel and Taylor, William R. and Ehrig, Rainald and Witaschek, Tom and Buttgereit, Frank}, title = {Objektive Quantifizierung der Morgensteifigkeit als Parameter f{\"u}r rheumatoide Arthritis im Metacarpophalangealgelenk}, series = {9. Jahrestagung der Deutschen Gesellschaft f{\"u}r Biomechanik (DGfB), Bonn}, booktitle = {9. Jahrestagung der Deutschen Gesellschaft f{\"u}r Biomechanik (DGfB), Bonn}, language = {de} } @inproceedings{TaylorFroehlichButtgereitetal.2012, author = {Taylor, William R. and Fr{\"o}hlich, Annika and Buttgereit, Frank and Ehrig, Rainald and Witaschek, Tom and Duda, Georg}, title = {Metacarpophalangeal joint stiffness is reduced in patients affected by rheumatoid arthritis after glucocorticoid medication}, series = {Proceedings of the ESM-2012, Aalborg}, booktitle = {Proceedings of the ESM-2012, Aalborg}, editor = {Kersting, Uwe and Morlock, Michael and Jirova-Enzmann, Daniela and Dremstrup, Kim}, publisher = {Department of Health Science and Technology, Aalborg University}, pages = {39}, year = {2012}, language = {en} } @article{WeberFischerDamerauetal., author = {Weber, Marie-Christin and Fischer, Lisa and Damerau, Alexandra and Ponomarev, Igor and Pfeiffenberger, Moritz and Gaber, Timo and G{\"o}tschel, Sebastian and Lang, Jens and R{\"o}blitz, Susanna and Buttgereit, Frank and Ehrig, Rainald and Lang, Annemarie}, title = {Macroscale mesenchymal condensation to study cytokine-driven cellular and matrix-related changes during cartilage degradation}, series = {Biofabrication}, volume = {12}, journal = {Biofabrication}, number = {4}, doi = {10.1088/1758-5090/aba08f}, abstract = {Understanding the pathophysiological processes of cartilage degradation requires adequate model systems to develop therapeutic strategies towards osteoarthritis (OA). Although different in vitro or in vivo models have been described, further comprehensive approaches are needed to study specific disease aspects. This study aimed to combine in vitro and in silico modeling based on a tissue-engineering approach using mesenchymal condensation to mimic cytokine-induced cellular and matrix-related changes during cartilage degradation. Thus, scaffold-free cartilage-like constructs (SFCCs) were produced based on self-organization of mesenchymal stromal cells (mesenchymal condensation) and i) characterized regarding their cellular and matrix composition or secondly ii) treated with interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) for 3 weeks to simulate OA-related matrix degradation. In addition, an existing mathematical model based on partial differential equations was optimized and transferred to the underlying settings to simulate distribution of IL-1β, type II collagen degradation and cell number reduction. By combining in vitro and in silico methods, we aim to develop a valid, efficient alternative approach to examine and predict disease progression and effects of new therapeutics.}, language = {en} } @article{WeberFischerDamerauetal., author = {Weber, Marie-Christin and Fischer, Lisa and Damerau, Alexandra and Ponomarev, Igor and Pfeiffenberger, Moritz and Gaber, Timo and G{\"o}tschel, Sebastian and Lang, Jens and R{\"o}blitz, Susanna and Buttgereit, Frank and Ehrig, Rainald and Lang, Annemarie}, title = {In vitro and in silico modeling of cellular and matrix-related changes during the early phase of osteoarthritis}, series = {BioRxiv}, journal = {BioRxiv}, doi = {10.1101/725317}, abstract = {Understanding the pathophysiological processes of osteoarthritis (OA) require adequate model systems. Although different in vitro or in vivo models have been described, further comprehensive approaches are needed to study specific parts of the disease. This study aimed to combine in vitro and in silico modeling to describe cellular and matrix-related changes during the early phase of OA. We developed an in vitro OA model based on scaffold-free cartilage-like constructs (SFCCs), which was mathematically modeled using a partial differential equation (PDE) system to resemble the processes during the onset of OA. SFCCs were produced from mesenchymal stromal cells and analyzed weekly by histology and qPCR to characterize the cellular and matrix-related composition. To simulate the early phase of OA, SFCCs were treated with interleukin-1β (IL-1β), tumor necrosis factor α (TNFα) and examined after 3 weeks or cultivated another 3 weeks without inflammatory cytokines to validate the regeneration potential. Mathematical modeling was performed in parallel to the in vitro experiments. SFCCs expressed cartilage-specific markers, and after stimulation an increased expression of inflammatory markers, matrix degrading enzymes, a loss of collagen II (Col-2) and a reduced cell density was observed which could be partially reversed by retraction of stimulation. Based on the PDEs, the distribution processes within the SFCCs, including those of IL-1β, Col-2 degradation and cell number reduction was simulated. By combining in vitro and in silico methods, we aimed to develop a valid, efficient alternative approach to examine and predict disease progression and new therapeutic strategies.}, language = {en} } @article{LangVolkamerBehmetal., author = {Lang, Annemarie and Volkamer, Andrea and Behm, Laura and R{\"o}blitz, Susanna and Ehrig, Rainald and Schneider, Marlon and Geris, Lisbet and Wichard, Joerg and Buttgereit, Frank}, title = {In silico Methods - Computational Alternatives to Animal Testing}, series = {ALTEX}, volume = {35}, journal = {ALTEX}, number = {1}, doi = {10.14573/altex.1712031}, pages = {126 -- 128}, abstract = {A seminar and interactive workshop on "In silico Methods - Computational Alternatives to Animal Testing" was held in Berlin, Germany, organized by Annemarie Lang, Frank Butt- gereit and Andrea Volkamer at the Charit{\´e}-Universit{\"a}tsmedizin Berlin, on August 17-18, 2017. During the half-day seminar, the variety and applications of in silico methods as alternatives to animal testing were presented with room for scientific discus- sions with experts from academia, industry and the German fed- eral ministry (Fig. 1). Talks on computational systems biology were followed by detailed information on predictive toxicology in order to display the diversity of in silico methods and the potential to embrace them in current approaches (Hartung and Hoffmann, 2009; Luechtefeld and Hartung, 2017). The follow- ing interactive one-day Design Thinking Workshop was aimed at experts, interested researchers and PhD-students interested in the use of in silico as alternative methods to promote the 3Rs (Fig. 2). Forty participants took part in the seminar while the workshop was restricted to sixteen participants.}, language = {en} } @article{LangHelfmeierStefanowskietal., author = {Lang, Annemarie and Helfmeier, Sarah and Stefanowski, Jonathan and Kuppe, Aditi and Sunkara, Vikram and Pfeiffenberger, Moritz and Wolter, Angelique and Damerau, Alexandra and Hemmati-Sadeghi, Shabnam and Ringe, Jochen and Haag, Rainer and Hauser, Anja E. and L{\"o}hning, Max and Perka, Carsten and Duda, Georg and Hoff, Paula and Schmidt-Bleek, Katharina and Gaber, Timo and Buttgereit, Frank}, title = {HIF-stabilization prevents delayed fracture healing}, series = {bioarxiv}, journal = {bioarxiv}, doi = {10.1101/2020.07.02.182832}, language = {en} } @article{LangFischerWeberetal., author = {Lang, Annemarie and Fischer, Lisa and Weber, Marie-Christin and Gaber, Timo and Ehrig, Rainald and R{\"o}blitz, Susanna and Buttgereit, Frank}, title = {Combining in vitro simulation and in silico modelling towards a sophisticated human osteoarthritis model}, series = {Osteoarthritis and Cartilage}, volume = {27}, journal = {Osteoarthritis and Cartilage}, doi = {10.1016/j.joca.2019.02.277}, pages = {S183}, abstract = {Our project aimed at building an in silico model based on our recently developed in vitro osteoarthritis (OA) model seeking for refinement of the model to enhance validity and translatability towards the more sophisticated simulation of OA. In detail, the previously 3D in vitro model is based on 3D chondrogenic constructs generated solely from human bone marrow derived mesenchymal stromal cells (hMSCs). Besides studying the normal state of the model over 3 weeks, the in vitro model was treated with interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNFα) to mimic an OA-like environment.}, language = {en} } @article{BoethDudaHinzmannetal., author = {Boeth, Heide and Duda, Georg and Hinzmann, Daniel and Hermann, Sandra and Taylor, William R. and Ehrig, Rainald and Witaschek, Tom and Buttgereit, Frank}, title = {A Novel Approach to Quantify Morning Stiffness in Patients with Rheumatoid Arthritis}, series = {Annual European Congress of Rheumatology, EULAR 2015, Rome}, journal = {Annual European Congress of Rheumatology, EULAR 2015, Rome}, language = {en} }